The present invention relates to a series of new epoxycarbacyclin derivatives, and provides a process for preparing these derivatives from Z-isomers of corresponding carbacyclin compounds and a process for converting these derivatives to the E-isomers of the corresponding carbocyclin compounds. Overall, the two processes of the invention enable the Z-isomer of a carbacyclin compound to be converted to its corresponding E-isomer in good yield.
Carbacyclin compounds are chemically stable and have been developed for various therapeutic uses, including the treatment of thrombosis. The compounds are produced by chemical synthesis and are normally obtained as mixtures of the E- and Z-isomers with respect to the exo double bond of the compound. For example, U.S. Pat. No. 4,322,435 discloses a series of carbacyclin derivatives, many of which have a double bond at the 5-position; during the synthesis of these compounds, the product is usually obtained as a mixture of the 5E- and 5Z-isomers. However, in general, the 5E-isomer is much more active and useful than its corresponding 5Z-isomer, which may have so little activity as to be of no practical use. Since, in the chemical synthesis of carbacyclin derivatives, a substantial proportion of the starting material is converted into the undesired 5Z-isomer (which substantially reduces the yield of 5E-isomer and hence increases the overall cost of the process), it is desirable to convert the unwanted 5Z-isomer to the valuable 5E-isomer.